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Abstract Purpose This study aims to understand the molecular mechanisms underlying the aging process and identify potential interventions to mitigate age-related decline and diseases. Methods This study utilized the GSE168753 dataset to conduct comprehensive differential gene expression analysis and co-expression module analysis. Machine learning and Mendelian randomization analyses were employed to identify core aging-associated genes and potential drug targets. Molecular docking simulations and mediation analysis were also performed to explore potential compounds and mediators involved in the aging process. Results The analysis identified 4164 differentially expressed genes, with 1893 upregulated and 2271 downregulated genes. Co-expression analysis revealed 21 modules, including both positively and negatively correlated modules between older age and younger age groups. Further exploration identified 509 aging-related genes with distinct biological functions. Machine learning and Mendelian randomization analyses identified eight core genes associated with aging, including DPP9, GNAZ, and RELL2. Molecular docking simulations suggested resveratrol, folic acid, and ethinyl estradiol as potential compounds capable of attenuating aging through modulation of RELL2 expression. Mediation analysis indicated that eosinophil counts and neutrophil count might act as mediators in the causal relationship between genes and aging-related indicators. Conclusion This comprehensive study provides valuable insights into the molecular mechanisms of aging and offers important implications for the development of anti-aging therapeutics. Key Messages What is already known on this topic – Prior research outlines aging’s complexity, necessitating precise molecular targets for intervention. What this study adds – This study identifies novel aging-related genes, potential drug targets, and therapeutic compounds, advancing our understanding of aging mechanisms. How this study might affect research, practice, or policy – Findings may inform targeted therapies for age-related conditions, influencing future research and clinical practices.
Yang et al. (Tue,) studied this question.